"Zip-to-Cytosol":Glutathione-Cleavable Fluorinated Polyplexes 在单位纳米剂量下提供siRNA,其基因沉默率高于90%
Yue Wang1, Jingyi Wang2, Hongyan Cui3
1Provincial Key Laboratory of Interdisciplinary Medical Engineering for Gastrointestinal Carcinoma, Cancer Hospital of Dalian University of Technology, No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, China.
Bioconjugate chemistry
|January 10, 2026
概括
一种新型的化多重复合平台 (PFND) 能够安全高效地传递小干扰RNA (siRNA). 与现有方法相比,这种先进的材料显示出优越的细胞吸收和基因沉默,为RNAi疗法提供了潜力.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 分子生物学分子生物学
背景情况:
- 开发小干扰RNA (siRNA) 的有效传递系统对于RNA干扰 (RNAi) 疗法至关重要.
- 现有的siRNA传递载体经常面临稳定性,细胞吸收和细胞内释放方面的挑战.
- 实现细胞外稳定性和细胞内有效载荷的快速释放仍然是一个重大障碍.
研究的目的:
- 开发一种新的化,二硫化物交联多重复合平台 (PFND),用于安全和强大的siRNA细胞质输送.
- 设计一个系统,使细胞外稳定与siRNA有效载荷的快速细胞内释放相协调.
- 与用于基因沉默应用的商业标准相比,评估PFND的有效性.
主要方法:
- 分支聚乙烯胺 (PEI) 的 perfluoro-acylation,以创建一个膜拉链骨干.
- 亚齐德和应力基因手柄的直角安装,用于使用siRNA进行无铜点击交叉链接.
- 多复合体大小,电荷,稳定性和拆卸动力学的特征.
- 在多个细胞系中细胞吸收,细胞毒性,血液溶解和基因沉默效率的体外评估.
主要成果:
- PFND多重复合 (60 nm,PDI < 0.1, ζ ≈ +22 mV) 在氨酸中表现出极好的稳定性,在氨酸中快速分解.
- 与Lipofectamine 3000相比,PFND在HeLa,HepG2和MDA-MB-468细胞中输送了2-3倍的siRNA,没有检测到血液溶解或细胞毒性.
- 通过PFND输送的10nMsiGAPDH实现了93%至98%的GAPDHmRNA沉默,显著优于黄金标准试剂的性能.
结论:
- 开发的PFND平台提供了一种安全且高效的细胞质siRNA输送方法.
- 独特的"外锁/内"设计有效平衡稳定性和可控释放.
- 对于高通量siRNA查和在基于RNAi的治疗中潜在的临床转化,PFND显示出显著的前景.
更多相关视频
09:09Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
7.9K
15:55Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
Published on: June 21, 2013
11.1K
相关概念视频
02:15Experimental RNAi
7.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
7.2K
02:30siRNA - Small Interfering RNAs
18.3K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
18.3K